Gene analysis of a patient with combined pituitary hormone deficiency

We encountered a 33-year-old woman with combined pituitary hormone deficiency. She had primary amenorrhea and was at Tanner stage 2 for both pubic hair and breast development. Her intelligence quotient, as determined by the Wechsler Adult Intelligence Scale, fourth edition, was 60, indicating mild intellectual disability. Based on endocrinological examinations, she was diagnosed with combined pituitary hormone deficiency (hypogonadotropic hypogonadism, growth hormone deficiency, and central hypothyroidism). Brain magnetic resonance imaging revealed anterior pituitary hypoplasia. There were no other abnormal intracranial findings, including those of the posterior pituitary and pituitary stalk. Her lack of secondary sexual characteristics made us suspect that genetic abnormalities may have contributed to her pituitary hormone deficiency. Therefore, we analyzed the coding and splicing regions of 17 major genes associated with congenital hypopituitarism (HESX1, LHX3, LHX4, OTX2, POU1F1, PROKR2, PROP1, SOX2, SOX3, CHD7, FGF8, FGFR1, GLI2, IGSF1, KISS1R, SOX10, and WDR11) using the NextSeq Sequencing System (Illumina, San Diego, CA, USA) at the Kazusa DNA Research Institute (Kisarazu, Japan).